A major goal of neurobiological research is the identification of neural mechanisms of associative learning. Recent cellular neurophysiological studies of learning in the relatively simple nervous systems of invertebrates have led to the identification of neural correlates of learning in primary sensory neurons. Several mechanisms have been proposed that may explain these examples of associative learning. The relationship between the behavior and biophysical changes produced by associative learning are currently under investigation. A mechanism of associative learning in the marine mollusk Hermissenda is being investigated using electrophysiological and biophysical techniques to study plasticity in sensory neurons. The hypothesis that is being examined is that learning involves alterations in intracellular calcium regulation. As a result of alterations in the regulation of intracellular Ca++, light results in a decrease in the amplitude of the generator potential. Photoreceptor desensitization is being used as a cellular probe to examine the effects under voltage clamp of Ca++ injection, Ca++ buffering (EGTA), and substances that effect Ca++ release and re-uptake. The regulation of Ca++ in this system may provide a useful model to study Ca++ effects on synaptic plasticity in other systems. The eventual analysis in a semi-intact preparation of cellular changes produced by learning will provide an experimental system for testing how a proposed mechanism of learning is responsible for the expression of behavior. Such a learning system will provide the opportunity to study the cellular and synaptic mechanisms of pharmacological agents that may effect learning and memory. This type of well-defined neural network that exhibits plasticity with learning may prove to be a useful model system for investigating problems of clinical relevance such as learning disorders during development and mental retardation.